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1.
Trends Genet ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38702264

RESUMO

Uncovering the genetic architectures of brain morphology offers valuable insights into brain development and disease. Genetic association studies of brain morphological phenotypes have discovered thousands of loci. However, interpretation of these loci presents a significant challenge. One potential solution is exploring the genetic overlap between brain morphology and disorders, which can improve our understanding of their complex relationships, ultimately aiding in clinical applications. In this review, we examine current evidence on the genetic associations between brain morphology and neuropsychiatric traits. We discuss the impact of these associations on the diagnosis, prediction, and treatment of neuropsychiatric diseases, along with suggestions for future research directions.

2.
Proc Natl Acad Sci U S A ; 121(24): e2317707121, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38830105

RESUMO

Human pose, defined as the spatial relationships between body parts, carries instrumental information supporting the understanding of motion and action of a person. A substantial body of previous work has identified cortical areas responsive to images of bodies and different body parts. However, the neural basis underlying the visual perception of body part relationships has received less attention. To broaden our understanding of body perception, we analyzed high-resolution fMRI responses to a wide range of poses from over 4,000 complex natural scenes. Using ground-truth annotations and an application of three-dimensional (3D) pose reconstruction algorithms, we compared similarity patterns of cortical activity with similarity patterns built from human pose models with different levels of depth availability and viewpoint dependency. Targeting the challenge of explaining variance in complex natural image responses with interpretable models, we achieved statistically significant correlations between pose models and cortical activity patterns (though performance levels are substantially lower than the noise ceiling). We found that the 3D view-independent pose model, compared with two-dimensional models, better captures the activation from distinct cortical areas, including the right posterior superior temporal sulcus (pSTS). These areas, together with other pose-selective regions in the LOTC, form a broader, distributed cortical network with greater view-tolerance in more anterior patches. We interpret these findings in light of the computational complexity of natural body images, the wide range of visual tasks supported by pose structures, and possible shared principles for view-invariant processing between articulated objects and ordinary, rigid objects.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Adulto , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Percepção Visual/fisiologia , Postura/fisiologia , Adulto Jovem , Imageamento Tridimensional/métodos , Estimulação Luminosa/métodos , Algoritmos
3.
J Biochem Mol Toxicol ; 38(4): e23698, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38501767

RESUMO

Accumulating evidence confirms that sleep insufficiency is a high risk factor for cognitive impairment, which involves inflammation and synaptic dysfunction. Resveratrol, an agonist of the Sirt1, has demonstrated anti-inflammation and neuroprotective effects in models of Alzheimer's disease, Parkinson's disease, and schizophrenia. However, the beneficial effects of resveratrol on sleep deprivation-induced cognitive deficits and its underlying molecular mechanisms are unclear. In the present study, thirty-two male C57BL/6 J mice were randomly divided into a Control+DMSO group, Control+Resveratrol group, SD+DMSO group, and SD+Resveratrol group. The mice in the SD+Resveratrol group underwent 5 days of sleep deprivation after pretreatment with resveratrol (50 mg/kg) for 2 weeks, while the mice in the SD+DMSO group only underwent sleep deprivation. After sleep deprivation, we evaluated spatial learning and memory function using the Morris water maze test. We used general molecular biology techniques to detect changes in levels of pro-inflammatory cytokines and Sirt1/miR-134 pathway-related synaptic plasticity proteins. We found that resveratrol significantly reversed sleep deprivation-induced learning and memory impairment, elevated interleukin-1ß, interleukin-6, and tumor necrosis factor-α levels, and decreased brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin levels by activating the Sirt1/miR-134 pathway. In conclusion, resveratrol is a promising agent for preventing sleep deprivation-induced cognitive dysfunction by reducing pro-inflammatory cytokines and improving synaptic function via the Sirt1/miR-134 pathway.


Assuntos
Disfunção Cognitiva , MicroRNAs , Masculino , Camundongos , Animais , Resveratrol/farmacologia , Privação do Sono/complicações , Privação do Sono/metabolismo , Sirtuína 1/metabolismo , Dimetil Sulfóxido/metabolismo , Dimetil Sulfóxido/farmacologia , Camundongos Endogâmicos C57BL , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Hipocampo/metabolismo , MicroRNAs/metabolismo , Citocinas/metabolismo , Cognição
4.
Neuroimage ; 269: 119928, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36740028

RESUMO

BACKGROUND: The cerebellum is recognized as being involved in neurocognitive and motor functions with communication with extra-cerebellar regions relying on the white matter integrity of the cerebellar peduncles. However, the genetic determinants of cerebellar white matter integrity remain largely unknown. METHODS: We conducted a genome-wide association analysis of cerebellar white matter microstructure using diffusion tensor imaging data from 25,415 individuals from UK Biobank. The integrity of cerebellar white matter microstructure was measured as fractional anisotropy (FA) and mean diffusivity (MD). Identification of independent genomic loci, functional annotation, and tissue and cell-type analysis were conducted with FUMA. The linkage disequilibrium score regression (LDSC) was used to calculate genetic correlations between cerebellar white matter microstructure and regional brain volumes and brain-related traits. Furthermore, the conditional/conjunctional false discovery rate (condFDR/conjFDR) framework was employed to identify the shared genetic basis between cerebellar white matter microstructure and common brain disorders. RESULTS: We identified 11 genetic loci (P < 8.3 × 10-9) and 86 genes associated with cerebellar white matter microstructure. Further functional enrichment analysis implicated the involvement of GABAergic neurons and cholinergic pathways. Significant polygenetic overlap between cerebellar white matter tracts and their anatomically connected or adjacent brain regions was detected. In addition, we report the overall genetic correlation and specific loci shared between cerebellar white matter microstructural integrity and brain-related traits, including movement, cognitive, psychiatric, and cerebrovascular categories. CONCLUSIONS: Collectively, this study represents a step forward in understanding the genetics of cerebellar white matter microstructure and its shared genetic etiology with common brain disorders.


Assuntos
Encefalopatias , Substância Branca , Humanos , Imagem de Tensor de Difusão , Estudo de Associação Genômica Ampla , Encéfalo , Anisotropia
5.
BMC Psychiatry ; 23(1): 859, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37985980

RESUMO

OBJECTIVE: Investigate the sleep characteristics of patients with obstructive sleep apnea syndrome (OSAS) comorbidity with panic disorder (PD), exploring its potential association with serum C-reactive protein (CRP) levels. PATIENTS AND METHODS: Fifty-four patients (25 OSAS patients with PD and 29 without PD) and 25 healthy controls (HCs) were included. The Self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Pittsburgh sleep quality index (PSQI) were used to assess the mood and sleep quality of the subjects. All patients had circulating CRP levels and polysomnography was performed. RESULTS: OSAS with PD had higher SAS, SDS, PSQI than the OSAS without PD. Compared to OSAS without PD, OSAS with PD had higher percentage of non- rapid eye movement sleep 1 and 2 (N1 and N2%), sleep latency, and a lower percentage of rapid eye movement sleep (REM%). Respiratory-related microarousal index, AHI, and time below 90% oxygen saturation (T90) were low, and the lowest oxygen saturation (LO2) was high. Serum CRP levels in OSAS patients with PD were lower than that in OSAS patients without PD, but higher than that in HCs. In OSAS patients with PD, serum CRP levels were negatively correlated with wake time after sleep onset and SAS scores but positively correlated with sleep efficiency and N2%. Serum CRP levels were positively correlated with T90 and negatively correlated with LO2. CONCLUSION: OSAS patients with PD had worse sleep quality, less severe OSAS, and low serum CRP levels. Serum CRP levels in OSAS patients with PD were associated with poorer sleep quality and duration of hypoxia rather than AHI.


Assuntos
Proteína C-Reativa , Transtorno de Pânico , Apneia Obstrutiva do Sono , Proteína C-Reativa/análise , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Humanos , Transtorno de Pânico/sangue , Respiração , Qualidade do Sono , Inflamação/metabolismo , Inflamação/patologia , Masculino , Feminino , Pessoa de Meia-Idade
6.
Environ Toxicol ; 38(11): 2668-2678, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37483094

RESUMO

The relationship between fine particulate matter (PM2.5) and chronic airway inflammatory diseases, such as chronic obstructive pulmonary disease and asthma, have garnered public attention, while the detailed mechanisms of PM2.5-induced airway inflammation remain unclear. This study reveals that PM2.5 induces airway inflammation both in vivo and in vitro, and, moreover, identifies DNA damage and DNA damage repair (DDR) as results of this exposure. Ataxia telangiectasia-mutated heterozygous (ATM+/- ) and wild-type C57BL/6 (WT) mice were exposed to PM2.5. The results show that, following exposure to PM2.5, the number of neutrophils in broncho alveolar lavage fluid and the mRNA expression of CXCL-1 in lung tissues of the ATM+/- mice were lower than those of the WT mice. The mRNA expression of FANCD2 and FANCI were also down-regulated. Human bronchial epithelial (HBE) cells were transfected with ATM-siRNA to induce down-regulation of ATM gene expression and were subsequently stimulated with PM2.5. The results show that the mRNA expression of TNF-α decreased in the ATM-siRNA-transfected cells. The mRNA expression of CXCL-1 and CXCL-2 in peritoneal macrophages, derived from ATM-null mice in which experiments showed that the protein expression of FANCD2 and FANCI decreased, were also decreased after PM2.5 exposure in ATM-siRNA-transfected HBE cells. In conclusion, PM2.5-induced airway inflammation is alleviated in ATM+/- mice compared with WT mice. ATM promotes PM2.5-induced airway inflammation, which may be attributed to the regulation of DNA damage and DDR.

7.
Clin Exp Immunol ; 208(1): 25-32, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35348596

RESUMO

Asthma and allergic rhinitis (AR) are widely considered to be the most common chronic inflammatory disorders. This study was performed to investigate the clinical features, disease severity, and upper airway inflammation among patients with asthma, AR, and asthma comorbid AR. Blood and nasal lavage fluid samples were collected from patients with isolated asthma (n = 23), isolated AR (n = 22), and asthma comorbid AR (n = 22). Demographic data, symptom evaluation, and spirometry were obtained from all subjects. The levels of interleukin (IL)-4, IL-5, IL-13, IL-17, IL-25, IL-33, and S100 proteins were measured in the nasal lavage fluid. Compared with isolated asthma, patients with asthma comorbid AR showed a lower quality of life according to the asthma quality-of-life questionnaire (AQLQ) score (6.11 ± 0.47 vs. 6.45 ± 0.35, P = 0.007). Additionally, no significant difference in the levels of IL-4 (P = 0.116), IL-25 (P = 0.235), and S100A12 (P = 0.392) was observed in nasal lavage fluid among three groups. However, miniscule levels of IL-5, IL-17, IL-13, IL-33, S100A8, and S100A9 were detected in nasal lavage fluid in all three groups. Patients with asthma comorbid AR showed an increased level of systemic cytokine in plasma than that of patients with isolated AR or asthma alone. The finding from our study may help clinicians to better understand the airway inflammation among asthma patients with or without AR.


Assuntos
Asma , Rinite Alérgica , Humanos , Interleucina-17 , Interleucina-33 , Interleucina-5 , Interleucina-13 , Qualidade de Vida , Asma/metabolismo , Inflamação
8.
J Vis ; 21(5): 7, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33961004

RESUMO

Despite the continuously changing visual inputs caused by eye movements, our perceptual representation of the visual world remains remarkably stable. Visual stability has been a major area of interest within the field of visual neuroscience. The early visual cortical areas are retinotopic-organized, and presumably there is a retinotopic to spatiotopic transformation process that supports the stable representation of the visual world. In this study, we used a cross-saccadic adaptation paradigm to show that both the orientation adaptation and face gender adaptation could still be observed at the same spatiotopic (but different retinotopic) locations even when the adapting stimuli were rendered invisible. These results suggest that awareness of a visual object is not required for its transformation from the retinotopic to the spatiotopic reference frame.


Assuntos
Retina , Movimentos Sacádicos , Adaptação Fisiológica , Movimentos Oculares , Humanos , Estimulação Luminosa
9.
BMC Neurol ; 18(1): 169, 2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30301456

RESUMO

BACKGROUND: POEMS syndrome is a rare neoplastic syndrome reflected by plasma cell disorder. It is composed by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. It is also reported to associate with Castleman disease. The early identification and treatment are pivotal to reduce the morbidity and mortality. CASE PRESENTATION: Here we report a 66-year-old man with treated Castleman disease developing with sequential presence of endocrinopathy polyneuropathy, skin changes, organomegaly and extravascular volume overload within 18 years, which was finally confirmed as POEMS syndrome by positive monoclonal protein. He was thereafter successfully treated with prednisone and azathioprine as primary therapy and thalidomide as maintenance therapy. CONCLUSION: The diagnosis of POEMS is based on a cluster of disorder involved in varied organs. We report a rare case that triggers the need to consider POEMS syndrome diagnosis for patients carrying Castleman disease and polyneuropathy.


Assuntos
Hiperplasia do Linfonodo Gigante/complicações , Síndrome POEMS/diagnóstico , Idoso , Humanos , Masculino
10.
J Asthma Allergy ; 17: 449-462, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38770268

RESUMO

Purpose: Little research has explored the proteomic characteristics of nasal lavage fluid from asthmatic patients. This study aims to investigate whether differentially expressed proteins (DEPs) in nasal lavage fluid can serve as a biomarker to differentiate asthma patients from healthy controls (HCs) and to discern between individuals with well controlled and poorly controlled asthma. Patients and Methods: We enrolled patients with allergic rhinitis (AR), asthma, or both conditions, and HCs in this study. We recorded patients' demographic and medical history data and administered asthma quality of life questionnaire (AQLQ) and asthma control questionnaire (ACQ). Nasal fluid samples were collected, followed by protein measurements, and proteomic analysis utilizing the data-independent acquisition (DIA) method. Results: Twenty-four with asthma, 27 with combined asthma+ AR, 25 with AR, and 12 HCs were enrolled. Four proteins, superoxide dismutase 2 (SOD2), serpin B7 (SERPINB7), kallikrein-13 (KLK13), and bleomycin hydrolase (BLMH) were significantly upregulated in nasal lavage fluid samples of asthma without AR, compared to HCs (Fold change ≥2.0, false-discovery rate [FDR] <0.05). Conversely, 56 proteins including secretoglobin family 2A member 1 (SCGB2A1) were significantly downregulated (fold change ≥2.0, FDR <0.05). Furthermore, 96.49% of DEPs including peptidase inhibitor 3 (PI3) and C-X-C motif chemokine 17 (CXCL17) were upregulated in poorly controlled asthma patients without AR relative those with well- or partly controlled asthma (fold change ≥1.5, FDR <0.05). Search tool for the retrieval of interacting genes/proteins (STRING) analysis showed that PI3, with 18 connections, may be pivotal in asthma control. Conclusion: The study revealed significant alteration in the nasal lavage proteome in asthma without AR patients. Moreover, our results indicated a potential association between the expression of proteome in the upper airway and the level of asthma control. Specifically, PI3 appears to be a key role in the regulation of asthma without AR.

11.
Mol Neurobiol ; 61(3): 1593-1604, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37736795

RESUMO

Previous in vitro and post-mortem studies have reported the role of inflammation in neurodegenerative disorders. However, the association between inflammation and brain structure in vivo and the transcriptome-driven functional basis with relevance to neurodegenerative disorders remains elusive. The aim of the present study is to identify the association among inflammation, brain structure, and neurodegenerative disorders at genetic and transcriptomic levels. Genetic variants associated with inflammatory cytokines were selected from the latest and largest genome-wide association studies of European ancestry. Neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and dementia with Lewy bodies (DLB) and brain structure imaging measures were selected as the outcomes. Two-sample Mendelian randomization analyses were conducted to identify the causal associations. Single-nucleus transcriptome data of the occipitotemporal cortex was further analyzed to identify the differential expressed genes in AD, which were tested for biological processes and protein interaction network. MR analysis indicated that genetically predicted TREM2 and sTREM2 were significantly associated with AD (TREM2: z-score = -9.088, p-value = 1.02 × 10-19; sTREM2: z-score = -7.495, p-value = 6.61 × 10-14). The present study found no evidence to support the causal associations between other inflammatory cytokines and the risks of AD, PD, ALS, or DLB. Genetically predicted TREM2 was significantly associated with the cortical thickness of inferior temporal (z-score = -4.238, p-value = 2.26 × 10-5) and pole temporal (z-score = -4.549, p-value = 5.40 × 10-6). In the occipitotemporal cortex samples, microglia were the main source of TREM2 gene and showed increasing expression of genes associated with inflammation and immunity. The present study has leveraged genetic and transcriptomic data to identify the association among TREM2, temporal lobe, and AD and the underlying cellular and molecular basis, thus providing a new perspective on the role of TREM2 in AD and insights into the complex associations among inflammation, brain structure, and neurodegenerative disorders, particularly AD.


Assuntos
Doença de Alzheimer , Esclerose Lateral Amiotrófica , Encefalite , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Esclerose Lateral Amiotrófica/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doenças Neurodegenerativas/genética , Doença de Parkinson/genética , Encéfalo/metabolismo , Inflamação/genética , Citocinas/genética , Citocinas/metabolismo
12.
J Neuroimmunol ; 386: 578252, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38086228

RESUMO

Growing evidence indicates that neuroinflammation plays a critical role in anxiety, depression, and cognitive impairment. Sleep loss disrupts the host's immune balance and increases neuroinflammation. This study explored whether chronic sleep deprivation aggravates lipopolysaccharide-induced anxiety, depression, and cognitive impairment and assessed the underlying mechanisms. Lipopolysaccharide (250 µg/kg) was administered to adult mice for 9 days, accompanied with daily intermittent sleep deprivation from 12:00 to 18:00 by using an activity wheel. Anxiety, depression, and cognitive function were evaluated using a task battery consisting of an open field, elevated plus maze, tail suspension, forced swimming, and Morris water maze tests. The levels of pro-inflammatory cytokines and synaptic plasticity-associated proteins were examined by enzyme-linked immunosorbent assay and western blot, respectively. The results showed that lipopolysaccharide increased anxiety- and depression-like behaviors, impaired cognitive function, uprelated interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and decreased brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD-95), and synaptophysin (SYN), which were aggravated by chronic sleep deprivation. These results suggest that chronic sleep deprivation exerted adverse effects on lipopolysaccharide-induced anxiety, depression, and cognitive impairment, which was associated with changes in pro-inflammatory cytokines and synaptic plasticity associated proteins.


Assuntos
Disfunção Cognitiva , Citocinas , Camundongos , Animais , Citocinas/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Depressão/induzido quimicamente , Depressão/metabolismo , Privação do Sono/complicações , Doenças Neuroinflamatórias , Disfunção Cognitiva/induzido quimicamente , Ansiedade/induzido quimicamente , Plasticidade Neuronal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Interleucina-6/metabolismo , Hipocampo
13.
Front Psychiatry ; 15: 1360305, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803679

RESUMO

Objectives: To examine serum concentrations of neurotensin, pannexin-1 and sestrin-2, and their correlations with subjective and objective sleep quality and cognitive function in the patients with chronic insomnia disorder (CID). Methods: Sixty-five CID patients were enrolled continuously and fifty-six good sleepers in the same period were served as healthy controls (HCs). Serum levels of neurotensin, pannexin-1 and sestrin-2 were measured by enzyme-linked immunosorbent assays. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and polysomnography, and mood was evaluated by 17-item Hamilton Depression Rating Scale. General cognitive function was assessed with the Chinese-Beijing Version of Montreal Cognitive Assessment and spatial memory was evaluated by Blue Velvet Arena Test (BVAT). Results: Relative to the HCs, the CID sufferers had higher levels of neurotensin (t=5.210, p<0.001) and pannexin-1 (Z=-4.169, p<0.001), and lower level of sestrin-2 (Z=-2.438, p=0.015). In terms of objective sleep measures, pannexin-1 was positively associated with total sleep time (r=0.562, p=0.002) and sleep efficiency (r=0.588, p=0.001), and negatively with wake time after sleep onset (r=-0.590, p=0.001) and wake time (r=-0.590, p=0.001); sestrin-2 was positively associated with percentage of rapid eye movement sleep (r=0.442, p=0.016) and negatively with non-rapid eye movement sleep stage 2 in the percentage (r=-0.394, p=0.034). Adjusted for sex, age and HAMD, pannexin-1 was still associated with the above objective sleep measures, but sestrin-2 was only negatively with wake time (r=-0.446, p=0.022). However, these biomarkers showed no significant correlations with subjective sleep quality (PSQI score). Serum concentrations of neurotensin and pannexin-1 were positively associated with the mean erroneous distance in the BVAT. Adjusted for sex, age and depression, neurotensin was negatively associated with MoCA score (r=-0.257, p=0.044), pannexin-1 was positively associated with the mean erroneous distance in the BVAT (r=0.270, p=0.033). Conclusions: The CID patients had increased neurotensin and pannexin-1 and decreased sestrin-2 in the serum levels, indicating neuron dysfunction, which could be related to poor sleep quality and cognitive dysfunction measured objectively.

14.
Nat Commun ; 15(1): 2819, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561338

RESUMO

Previous genetic studies of venous thromboembolism (VTE) have been largely limited to common variants, leaving the genetic determinants relatively incomplete. We performed an exome-wide association study of VTE among 14,723 cases and 334,315 controls. Fourteen known and four novel genes (SRSF6, PHPT1, CGN, and MAP3K2) were identified through protein-coding variants, with broad replication in the FinnGen cohort. Most genes we discovered exhibited the potential to predict future VTE events in longitudinal analysis. Notably, we provide evidence for the additive contribution of rare coding variants to known genome-wide polygenic risk in shaping VTE risk. The identified genes were enriched in pathways affecting coagulation and platelet activation, along with liver-specific expression. The pleiotropic effects of these genes indicated the potential involvement of coagulation factors, blood cell traits, liver function, and immunometabolic processes in VTE pathogenesis. In conclusion, our study unveils the valuable contribution of protein-coding variants in VTE etiology and sheds new light on its risk stratification.


Assuntos
Tromboembolia Venosa , Humanos , Tromboembolia Venosa/genética , Fatores de Risco , Fatores de Coagulação Sanguínea/genética , Exoma , Estudo de Associação Genômica Ampla , Fatores de Processamento de Serina-Arginina/genética , Fosfoproteínas/genética
15.
Sleep Med ; 117: 162-168, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38547593

RESUMO

BACKGROUND AND OBJECTIVE: Rumination, a common factor of chronic insomnia disorder (CID) caused by cognitive-emotional arousal, is associated with an increased amount of rapid eye movement (REM) sleep. However, the specific subtypes, such as phasic REM and tonic REM, that contribute to the increased REM sleep have not been reported. This study aimed to determine the association between rumination and different REM sleep subtypes in patients with CID. METHODS: This study enrolled 35 patients with CID and 27 age- and sex-matched healthy controls. The Immersion-Rumination Questionnaire evaluated participants' rumination, and the Insomnia Severity Index was used to assess insomnia severity. Finally, polysomnography was used to monitor objective sleep quality and quantification of different types of REM. RESULTS: The CID patients had higher rumination scores than the healthy controls. They had a shorter REM sleep duration, less phasic REM, a lower percentage of phasic REM time, and a higher percentage of tonic REM time. Spectral analysis revealed that the patients affected by insomnia had higher ß power during REM sleep, higher ß and σ power during phasic REM sleep, and higher ß, and γ power during tonic REM sleep. Partial correlation analysis showed that rumination in the CID patients correlated negatively with the duration of phasic REM sleep. Additionally, rumination correlated negatively with δ power in REM sleep and positively with ß power in REM sleep, tonic REM sleep, phasic REM sleep, N3and N2 sleep in the patients with CID. CONCLUSION: The CID patients had stronger rumination, reduced total and phasic REM sleep, and the stronger rumination was, the shorter phasic REM was and the higher fast (ß) wave power in REM sleep.


Assuntos
Transtorno do Comportamento do Sono REM , Distúrbios do Início e da Manutenção do Sono , Humanos , Sono REM , Distúrbios do Início e da Manutenção do Sono/complicações , Polissonografia , Nível de Alerta , Transtorno do Comportamento do Sono REM/complicações
16.
Sleep Med ; 117: 177-183, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554533

RESUMO

OBJECTIVES: To explore the relationship between nocturnal levels of stress-related hormones and different sleep-wake states in chronic insomnia disorder (CID) patients. METHODS: Thirty-three CID patients and 34 good sleepers were enrolled and completed assessment of sleep log, Pittsburgh Sleep Quality Index and Insomnia Severity Index. During a-overnight polysomnography monitoring, the patients' vein bleeds were continually collected at different time points (pre-sleep, deep-sleep, 5-min or 30-min waking, and morning waking-up). The control subjects' bleeds were collected only at 22:00 and morning waking-up. The serum hormones were detected using enzyme-linked immunosorbent assay. RESULTS: Compared with at pre-sleep, the level of cortisol was significantly higher at morning waking-up respectively in two-group subjects (Ps < 0.001), with insignificant inter-group differences in cortisol, corticotropin releasing hormone and copeptin at the two time-points. In the patients, the nocturnal secretion curves of three hormones were similar, with the highest concentration at morning waking-up, followed by 30-min waking, 5-min waking, pre-sleep, and deep-sleep. The patients' cortisol (Z = 79.192, P < 0.001) and copeptin (Z = 12.333, P = 0.015) levels were statistically different at different time-points, with higher cortisol at morning waking-up relative to deep-sleep, pre-sleep and 5-min waking (Ps < 0.05), and at 30-min waking relative to deep-sleep and pre-sleep (Ps < 0.05), and higher copeptin at morning waking-up relative to deep-sleep (P < 0.05). CONCLUSIONS: In CID, the nocturnal wakes were instantaneously accompanied by high level, and deep sleep was accompanied by the lowest levels, of stress-related hormones, especially in cortisol, supporting the insomniac hypothesis of increased nocturnal pulse-release of cortisol.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Humanos , Projetos Piloto , Hidrocortisona , Sono , Polissonografia
17.
Brain Behav ; 14(5): e3515, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38702895

RESUMO

INTRODUCTION: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown. METHODS: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting. RESULTS: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. CONCLUSIONS: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.


Assuntos
Hipocampo , Melatonina , Transtornos da Memória , Plasticidade Neuronal , Privação do Sono , Animais , Melatonina/farmacologia , Melatonina/administração & dosagem , Privação do Sono/complicações , Privação do Sono/tratamento farmacológico , Privação do Sono/fisiopatologia , Camundongos , Masculino , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Feminino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Plasticidade Neuronal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Gravidez , Privação Materna , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico
18.
Geroscience ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822946

RESUMO

Considerable uncertainty remains regarding the associations of multiple factors with brain health. We aimed to conduct an exposome-wide association study on neurodegenerative disease and neuropsychiatry disorders using data of participants from the UK Biobank. Multivariable Cox regression models with the least absolute shrinkage and selection operator technique as well as principal component analyses were used to evaluate the exposures in relation to common disorders of central nervous system (CNS). Restricted cubic splines were conducted to explore potential nonlinear correlations. Then, weighted standardized scores were generated based on the coefficients to calculate the joint effects of risk factors. We also estimated the potential impact of eliminating the unfavorable profiles of risk domains on CNS disorders using population attributable fraction (PAF). Finally, sensitivity analyses were performed to reduce the risk of reverse causality. The current study discovered the significantly associated exposures fell into six primary exposome categories. The joint effects of identified risk factors demonstrated higher risks for common disorders of CNS (HR = 1.278 ~ 3.743, p < 2e-16). The PAF varied by exposome categories, with lifestyle and medical history contributing to majority of disease cases. In total, we estimated that up to 3.7 ~ 64.1% of disease cases could be prevented.This study yielded modifiable variables of different categories and assessed their joint effects on common disorders of CNS. Targeting the identified exposures might help formulate effective strategies for maintaining brain health.

19.
Nat Hum Behav ; 8(6): 1194-1208, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38589703

RESUMO

While numerous genomic loci have been identified for neuropsychiatric conditions, the contribution of protein-coding variants has yet to be determined. Here we conducted a large-scale whole-exome-sequencing study to interrogate the impact of protein-coding variants on 46 neuropsychiatric diseases and 23 traits in 350,770 adults from the UK Biobank. Twenty new genes were associated with neuropsychiatric diseases through coding variants, among which 16 genes had impacts on the longitudinal risks of diseases. Thirty new genes were associated with neuropsychiatric traits, with SYNGAP1 showing pleiotropic effects across cognitive function domains. Pairwise estimation of genetic correlations at the coding-variant level highlighted shared genetic associations among pairs of neurodegenerative diseases and mental disorders. Lastly, a comprehensive multi-omics analysis suggested that alterations in brain structures, blood proteins and inflammation potentially contribute to the gene-phenotype linkages. Overall, our findings characterized a compendium of protein-coding variants for future research on the biology and therapeutics of neuropsychiatric phenotypes.


Assuntos
Sequenciamento do Exoma , Transtornos Mentais , Humanos , Transtornos Mentais/genética , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Predisposição Genética para Doença , Reino Unido , Fenótipo , Doenças Neurodegenerativas/genética , Estudos de Associação Genética , Idoso , Exoma/genética
20.
Nat Hum Behav ; 8(4): 779-793, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38182882

RESUMO

Despite its crucial role in the regulation of vital metabolic and neurological functions, the genetic architecture of the hypothalamus remains unknown. Here we conducted multivariate genome-wide association studies (GWAS) using hypothalamic imaging data from 32,956 individuals to uncover the genetic underpinnings of the hypothalamus and its involvement in neuropsychiatric traits. There were 23 significant loci associated with the whole hypothalamus and its subunits, with functional enrichment for genes involved in intracellular trafficking systems and metabolic processes of steroid-related compounds. The hypothalamus exhibited substantial genetic associations with limbic system structures and neuropsychiatric traits including chronotype, risky behaviour, cognition, satiety and sympathetic-parasympathetic activity. The strongest signal in the primary GWAS, the ADAMTS8 locus, was replicated in three independent datasets (N = 1,685-4,321) and was strengthened after meta-analysis. Exome-wide association analyses added evidence to the association for ADAMTS8, and Mendelian randomization showed lower ADAMTS8 expression with larger hypothalamic volumes. The current study advances our understanding of complex structure-function relationships of the hypothalamus and provides insights into the molecular mechanisms that underlie hypothalamic formation.


Assuntos
Estudo de Associação Genômica Ampla , Hipotálamo , Humanos , Hipotálamo/metabolismo , Hipotálamo/diagnóstico por imagem , Masculino , Feminino , Adulto , Transtornos Mentais/genética , Proteínas ADAMTS/genética , Pessoa de Meia-Idade , Análise da Randomização Mendeliana
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